|Year : 2019 | Volume
| Issue : 2 | Page : 81-87
Prophylactic administration of two different bolus doses of phenylephrine for prevention of spinal-induced hypotension during cesarean section: A prospective double-blinded clinical study
Sawai Singh Jaitawat, Seema Partani, Venus Sharma, Karishma Johri, Sunanda Gupta
Department of Anaesthesiology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India
|Date of Submission||23-Apr-2019|
|Date of Acceptance||05-May-2019|
|Date of Web Publication||06-Sep-2019|
Dr. Seema Partani
14 Nakoda Complex Hiran Magri Sector 4, Udaipur - 313 001, Rajasthan
Source of Support: None, Conflict of Interest: None
Background: Hypotension following spinal anesthesia during cesarean delivery can cause adverse maternal and fetal effects. Phenylephrine has been found to be a potent vasopressor in preventing spinal-induced hypotension during cesarean section (CS) without fetal acidosis. Material and Methods: In this prospective double-blinded study, 120 parturients of ASA grade I and II posted for CS under spinal anesthesia were randomized into three groups of 40 each: group P0, group P75, and group P100. The primary objective was to study the influence of two different doses of phenylephrine on the incidence of spinal-induced hypotension during cesarean section. Corelation of postural variations in baseline hemodynamic data with observed degree of orthostatic hypotension to predict intraoperative hypotension, requirement of rescue vasopressors, and incidence of side effects and neonatal outcome were the secondary outcome measures. Statistical analysis was done with SPSS version 16 using student t test, ANOVA, and Chi-square test. Results: Incidence of hypotension was 70%, 25%, and 17.50% in P0, P75, and P100 groups (P < 0.001), respectively. Maximum change in systolic blood pressure paralleled the increasing doses of prophylactic phenylephrine which was highest in P100 group as compared to P75 and P0 groups. Incidence of bradycardia was higher in group P100 than groups P75 and P0. There were no other significant differences among the three groups. Conclusion: Prophylactic bolus dose of phenylephrine 75 mcg was found to be effective for the management of spinal-induced hypotension and should be preferred over 100 mcg which causes significant bradycardia and reactive hypertension.
Keywords: Cesarean delivery, optimum dose, phenylephrine, spinal hypotension
|How to cite this article:|
Jaitawat SS, Partani S, Sharma V, Johri K, Gupta S. Prophylactic administration of two different bolus doses of phenylephrine for prevention of spinal-induced hypotension during cesarean section: A prospective double-blinded clinical study. J Obstet Anaesth Crit Care 2019;9:81-7
|How to cite this URL:|
Jaitawat SS, Partani S, Sharma V, Johri K, Gupta S. Prophylactic administration of two different bolus doses of phenylephrine for prevention of spinal-induced hypotension during cesarean section: A prospective double-blinded clinical study. J Obstet Anaesth Crit Care [serial online] 2019 [cited 2019 Nov 12];9:81-7. Available from: http://www.joacc.com/text.asp?2019/9/2/81/266140
| Introduction|| |
Spinal-induced hypotension caused by sympathetic neuronal block during cesarean delivery remains a significant clinical challenge. Maternal symptoms like nausea, vomiting, dyspnea, and adverse fetal effects including depressed APGAR scores have been correlated with the severity and duration of hypotension. According to the international consensus statement on the management of hypotension with vasopressors, the aim should be to maintain the baseline systolic arterial pressure (SAP) at ≥90% before spinal anesthesia and avoid a baseline decrease of <80%. Although, in addition to nonpharmacological methods, prophylactic use of vasopressors has been recommended to prevent or treat spinal-induced hypotension, consensus on the ideal vasopressor is still debated. While vasopressors with α-agonist activity have been considered the most appropriate till date, recent researches have shown that an added β-agonist activity may prove to be more effective (noradrenaline, metaraminol)., Phenylepherine has been considered the preferred vasopressor in parturients due to its faster onset, minimal placental passage, and less incidence of fetal acidosis and maternal nausea and vomiting.,,, It is a direct sympathomimetic agent with selective α-adrenergic activity and is easy to titrate while maintaining maternal blood pressure without producing undue tachycardia.
The autonomic nervous system plays a pivotal role in the adaptation of the cardiovascular system to various hemodynamic requirements. Standing in supine position causes the blood to be pulled from thorax into the lower extremity veins causing a decrease in blood pressure and stimulating the baroreceptors, thus increasing the heart rate (HR)., It can be postulated that orthostatic cardiovascular reflexes in pregnancy might be used to identify patients at risk of hypotension following spinal anesthesia. Pregnant women with a higher baseline HR may be associated with higher intrinsic sympathetic tone and might prove to be at a greater risk for spinal hypotension. Strong evidence suggests that cardiac output correlates more closely with uteroplacental blood flow rather than systemic blood pressure measurements. Phenylephrine bolus doses were found to be the most appropriate method of intervention to restore systemic vascular resistance and cardiac output. As the HR is a surrogate marker for cardiac output, it has been used as a predictor of spinal hypotension. This is even more pertinent in the poor resource setting, where targeting simple surrogate outcomes such as HR could be explored for practical implementation in clinical guidelines.
Various studies have been carried out to evaluate the optimum doses of phenylephrine (20 μg to 100 μg). While a dose of 20 μg has been found to be ineffective, doses as high as 100 μg were found to cause reflex maternal bradycardia. Our aim was to find out the optimum dose of phenylephrine which would maintain hemodynamic stability without compromising cardiac output.
The primary objective of the study was to compare the effects of prophylactic administration of two different doses of phenylephrine on the incidence of spinal-induced hypotension during cesarean section. The secondary outcome measures were to study the correlation of baseline hemodynamic data with observed degree of hypotension in an attempt to predict intraoperative hypotension, requirement of rescue vasopressors, and incidence of adverse effects and neonatal outcomes.
| Material and Methods|| |
This prospective double-blinded study was conducted at a tertiary care centre between January 2016 and June 2017. We enrolled 120 parturients of American Society of Anesthesiologists (ASA) grade I or II between 18 to 35 years of age and posted for elective cesarean delivery under spinal anesthesia. Parturients with complications like risk of excessive bleeding (placenta previa, prolonged labor, abnormal presentation, multiple gestation) pre-existing or pregnancy-induced hypertension, cardiovascular disease, cerebrovascular disease, severe anemia, diabetes, multiple gestation, known fetal abnormality, contraindication for spinal anesthesia, known allergy to phenylephrine, maternal systolic blood pressure (SBP) <100 mm Hg, and inability or refusal to give informed consent were excluded from the study. The study was approved by the Institutional Research Ethics Board and informed consent was obtained from all the patients.
Randomization was performed using computer-generated random number table. Parturients were randomly allocated into three groups of 40 each to receive either saline (group P0), phenylephrine 75 mcg (group P75), or phenylephrine 100 mcg (group P100). Group assignments were sealed with in opaque envelopes and were opened by the principal anesthesiologist just before the administration of subarachnoid block (SAB) to the patient. Another anesthesiologist who was not involved in the study prepared the phenylephrine dose according to the randomization group. Parturients and principal anesthesiologists who monitored and recorded the hemodynamic parameters were blinded to the group assignment.
Following preanesthetic evaluation, all the parturients received oral ranitidine (150 mg) the night before and the morning of the day of surgery with a sip of water. Then, through an 18-gauge cannula, lactated Ringer's solution was infused at the rate of 10 ml/kg/hour in the preoperative room and IV injection of ondansetron 4 mg were administered as premedications. The SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), and HR were measured at 1-minute intervals using an automated noninvasive monitor in both supine and standing positions. A total of six recordings were taken (three in supine and three in standing) and an average of the three readings in each position was taken preoperatively to test the orthostatic cardiovascular reflexes with change in position. Any parturient developing <20% baseline SBP were infused with crystalloids at 15 ml/kg/hr. Once the parturient was hemodynamically stable, she was shifted into the operation theatre.
In the operating room, standard monitoring included pulse oximetry, electrocardiogram, and noninvasive blood pressure. The patient was placed in the left lateral position, skin was decontaminated with povidione iodine, and a standard dose of 12.5 mg of 0.5% bupivacaine heavy was administered in the subarachnoid space (L3-L4 or L2-L3) using a 25-gauge Quincke needle. Another anesthesiologist blinded to the group allocation, administered the study drug intravenously immediately after the spinal injection at time 0.
Hypotension (fall in SBP to less than 20% of baseline) was treated with maximum two doses of phenylephrine (100 μg) and, if hypotension persisted or bradycardia occurred, another rescue vasopressor (ephedrine 6 mg IV bolus) was administered. Bradycardia (HR less than 55 beats per minute) was treated with an IV bolus of atropine sulfate (0.6 mg). Demographic and obstetric data like age, weight, parity, gestation week, total fluids, and duration of surgery and anesthesia were noted in a structured proforma. Block height was assessed bilaterally by using pin prick technique at 5-min intervals for the first 15 min following spinal anesthesia. Surgery was allowed if block height reached the T6 dermatome. If the block height failed to reach the T6 dermatome, then IV analgesics (fentanyl 25 mcg, ketamine 20 mg) were given and the patients were withdrawn from the study. Hemodynamic data (HR, SBP, DBP, and MAP) were recorded from the time of spinal injection and subsequently at every 2-min interval for 10 min and then every 5 min upto 30 min or till the end of surgery. The time of first rescue vasopressor, total number of doses required, and the total dose of vasopressors used to treat the first hypotensive episode along with dose of rescue vasopressor (ephedrine) required were noted. The number of patients developing bradycardia (<55 bpm) were noted and treated with IV atropine 0.6 mg. Adverse effects like nausea, vomiting, shortness of breath, and chest pain were recorded. In addition, the total duration of surgery and anesthesia, total fluid required during surgery along with APGAR score at 1 min and 5 min, requirement of neonatal intensive care, and the weight of baby were also recorded.
The sample size was based on the assumption that a 75% to 85% frequency of spinal-induced hypotension during CS could be detected. For a power of 85% and an α error of 0.05, a sample size of 40 patients in each group was considered appropriate.
Statistical analysis was done using SPSS (version 16) software. Analysis of variance (ANOVA) was used to find the significance between the three groups for continuous variables and paired t-test was used for intragroup comparison. Chi-square test was used to find the significance of study parameters on a categorical scale. Results were expressed as mean ± standard deviation and P< 0.05 was considered statistically significant.
| Results|| |
A total of 120 patients were enrolled and randomized into three groups of 40 each. Since only those parturients who achieved adequate block height (T6) were included in the study, there were no dropouts in the study. Demographic and obstetric data such as age, weight of mother, gestation week, parity, and duration of surgery and anesthesia were comparable in all the three groups. The total fluid requirement of the control group was significantly more (P < 0.001) as compared to the other two groups [Table 1]. In an attempt to predict intraoperative hypotension among the parturients, analysis of the orthostatic challenge and the change the position from supine to standing did not result in any statistically significant change in the hemodynamic parameters in any of the three groups (P > 0.05).
Incidence of hypotension was significantly (P < 0.001) more in the control group (70%) than groups P75 (25%) and P100 (17.50%) [Table 2]. A significant fall in SBP, DBP, MAP was observed in the control group in the intraoperative period; however, incidence of hypotension between groups P75 and P100 were comparable (P > 0.05). Increase in SBP was observed in P100 group which was maximum at 6 min–10 min following spinal block and was found to be statistically significant (P < 0.05) [Figure 1] and [Figure 2]. The need for administering rescue vasopressors was significantly delayed in groups P75 (9.73 ± 4.54 min) and P100 (11.71 ± 4.46 min) as compared to the control group (7.39 ± 3.59 min; P< 0.001). The total dose volume (mg) and the number of doses of phenylephrine were significantly higher in the control group than in the groups P75 and P100 (P < 0.001) [Table 2].
|Figure 1: Trends in systolic blood pressure and diastolic blood pressure in all groups|
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The P100 group showed a significant fall in HR from baseline after 4 min of SAB and remained significantly low throughout the intraoperative period (p < 0.001) [Figure 3]. The mean value of lowest HR (bpm) was highly significant in P100 (59.78 ± 4.98) as compared to P75 (68.33 ± 6.85) and P0 (77.60 ± 8.10) (P < 0.001) [Table 3]. The number of doses of atropine and the total dose volume was higher in P100 group as compared to the other two groups (P < 0.001). Higher incidence of bradycardia was observed in group P100 (37.5%) than P75 (15%) and control group (10%) (P < 0.001) [Table 4]. There was no significant difference in the incidence of nausea, vomiting, headache, APGAR scores, and need for neonatal intensive care (P > 0.05).
| Discussion|| |
Untreated maternal hypotension following spinal anesthesia is detrimental as it causes both maternal and fetal adverse effects. Various guidelines suggest maintenance of SBP at 100% of baseline with liberal use of vasopressors., According to NICE clinical guidelines, women undergoing LSCS should receive prophylactic IV ephedrine or phenylephrine and volume preloading to reduce the risk of hypotension. Moreover, the American Society of Anesthesiologists (ASA) guidelines for obstetric anesthesia recommends no delay in administering spinal anesthesia for cesarean delivery to administer a fixed volume of fluid and IV ephedrine or phenylephrine to treat spinal hypotension. However, the ideal vasopressor used to maintain uterine perfusion has been an area of intense research for several decades. Because uteroplacental blood flow lacks autoregulation, it is directly dependent on uterine perfusion pressure and is inversely proportional to uterine vascular resistance. Notably, most research comparing vasopressor therapy for cesarean delivery has been done in healthy women undergoing elective cesarean delivery. Experts conclude that the efficacy and safety of phenylephrine makes it superior for systemic vascular resistance restoration after spinal anesthesia and should be preferred in the absence of maternal bradycardia as it improves the acid-base status in uncomplicated pregnancies.,, Although phenylephrine can be administered either as bolus or infusion, a prophylactic bolus strategy has been shown to be superior to a therapeutic bolus strategy with regards to incidence of hypotension, nausea, and vomiting.,,, In resource poor setting and for all emergency cesarean sections, administering a bolus dose of prophylactic phenylephrine is safe and practical for managing post-spinal hypotension., The present study was designed with two different prophylactic bolus doses of phenylephrine to find out the optimum dose which will prevent spinal hypotension without any maternal and fetal adverse effects.
In our study, all groups were comparable regarding age, weight of mother, gestation week, parity, and duration of surgery. The total IV fluids administered were significantly more in control group (13450 ± 201.2 ml) as compared to the other two groups P75 (1200.0 ± 161.72 ml) and P100 (1170.0 ± 182.8 ml) (P < 0.001). Increased fluid requirement of the control group could be attributed to the effect of therapeutic (control group) versus prophylactic (study group) bolus doses of vasopressor on incidence of hypotension [Table 1] and [Table 2]. Similarly, Lee HM et al. also observed slightly more requirement of fluids in the control group (900 ml) than the study group (800 ml; phenylephrine 1.5 mg/kg prophylactically). Although it had no statistical significance, it can be attributed to the increased incidence of hypotension in control group (71.7%) which increased the volume of total fluids infused as compared to the study group (37%).
Various factors related to predicting spinal hypotension include increased body mass index, inadequate weight gain during pregnancy, advanced age, increased preoperative HR along with tests like positive supine stress test, orthostatic hypotension., The perfusion index, pleth variability index, HR and parameters of HR variability as measured by pulse oximetry have also been found to predict hypotension. In our study, we compared positional variations of hemodynamic data with incidence of hypotension for prediction of post-spinal hypotension and found no statistically significant difference among the groups (P > 0.05). Hence, we could not analyze these data for predicting intraoperative hypotension. Similarly, Frollich et al. observed no significant correlation in orthostatic change of blood pressure and intraoperative hypotension as measured by ephedrine requirement; however, they found significant positive correlation between increased baseline HR and ephedrine requirement (P = 0.005). A study by Kinsella et al. to predict hypotension during CS using a orthostatic challenge (tilt test) found that cardiovascular responses to the change from recumbent to sitting position were not useful as a predictor of hypotension.
Although only very few studies have investigated prophylactic bolus regimen to find out the optimum dose of phenylephrine, current evidence supports use of prophylactic phenylephrine titrated to maintain blood pressure near baseline (the usual dose range is 25 to 100 μg/min).,,,,,,, Das Neves et al. compared three different regimens in parturients for cesarean section: continuous infusions (0.15 μg/kg/min) versus prophylactic bolus (50 μg) versus therapeutic bolus (50 μg) and the incidence of hypotension was found to be 17.5%, 32.5%, and 85%, respectively. Although results for preventing hypotension were more effective in the continuous infusion group, prophylactic bolus dose was also found to be effective in preventing hypotension. Tanaka et al. reported the ED95 of prophylactic bolus of phenylephrine as 122 μg. They found that lower doses (60–80 μg) may not be as effective as larger doses (90–120 μg) in preventing hypotension. However, in our study, both 75 μg and 100 μg were comparative in preventing hypotension.
In the present study, incidence of hypotension was 70% in control group, 25%in group P75, and 17.50% in P100 group which was statistically significant when compared to control group (P < 0.001); however, it was found to be comparable between group P75 and P100(P > 0.05). Requirement of phenylephrine in terms of number of doses and total dose in control group was significantly higher than P75 and P100 group (P < 0.001). The use of first rescue vasopressor was earlier in the control group (7.39 ± 3.59 min) as compared to P75 group (9.73 ± 4.54 min) and P100 group (11.71 ± 4.46 min) which was statistically significant (P < 0.001). Similarly, Siddik Sayyid et al. (2014) and Lee HM et al. reported that the incidence of hypotension was significant in the groups that did not receive any prophylactic phenylephrine., Incidence of increase in blood pressure was observed more in P100 group during 6 to 10 min of intraoperative period in our study (P < 0.001). This could be attributed to the stimulation of postsynaptic α receptors by phenylephrine resulting in intense arterial and peripheral vasoconstrictions causing rise in blood pressure. Lee HM et al. also found increased incidence of hypertension with increase in doses of prophylactic phenylephrine (1 μgm/kg: 6.7%, 1.5 μgm/kg: 10.9%, 2 μgm/kg: 37.0%) (P < 0.001), which is in accordance to our study. In addition, several other studies have also reported increased episodes of hypertension in patients receiving phenylephrine at higher infusion rates as compared to low infusion rates., Some patients experienced bradycardia and hypertension even at lower infusion rates which suggests that bolus administration of phenylephrine titrated as required in the individual case maybe a better option than prophylactic infusion.
In this study, there was significant reduction in the HR after the administration of bolus dose phenylephrine. The intraoperative HR changes were statistically significant between the three groups (P < 0.001). In addition, incidence of bradycardia and total rescue dose of atropine were significantly high (P < 0.001) in group P100 which can be attributed to the dose-dependent effect of phenylephrine on HR. Similarly, a significant concentration-dependent reduction in HR (linear trend; P < 0.007) has been observed by Stewert et al. In a systematic review of randomized controlled trials, Lee HM et al. concluded that the women receiving phenylephrine were more likely to develop bradycardia (<50 bpm) as compared to those treated with ephedrine. In the present study, incidence of nausea and vomiting (P0: 10%;P75: 20%; P100: 12.5%- P > 0.05) was comparable in all the three groups, with no correlation to different doses of phenylephrine. There was no statistical difference in the APGAR scores at 1 min and 5 min among the three groups.
Limitations of the study
Advanced computerized noninvasive cardiac output monitors could give a better estimate of the hemodynamic variations as compared to surrogate markers like HR, HR variability, and blood pressures. Umbilical cord blood gas estimation could have given a much better analysis of neonatal status and outcome. In this study, we did not observe and record the hemodynamic effects of oxytocin and hence we could not correlate the individual cardiovascular effects of phenylephrine and oxytocin.
| Conclusion|| |
Prophylactic administration of bolus phenylephrine significantly decreases the incidence of maternal hypotension and a dose of 75 μg is adequate to prevent post-spinal hypotension for cesarean delivery without any detrimental effect on the neonatal and maternal outcomes.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]